4-chloro-2,6-diaminopyrimidine

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

November 2015

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference 1

Reference Type:

other: QMRF

Title:

Unnamed

Year:

2015

Report date:

2015

Reference 2

Reference Type:

other: QPRF

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Guideline:

other: REACH guidance on QSARs R.6 May/July 2008

Principles of method if other than guideline:

Model or submodel name: ACD/Percepta model for acute aquatic toxicity in
Daphnia magna.
Model version: ACD labs/Percepta (2014 Release).

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-2,6-diaminopyrimidine

EC Number:

205-863-9

EC Name:

4-chloro-2,6-diaminopyrimidine

Cas Number:

156-83-2

Molecular formula:

C4H5ClN4

IUPAC Name:

6-chloropyrimidine-2,4-diamine

Details on test material:

SMILES: Clc1cc(N)nc(N)n1
InChI: InChI=1S/C4H5ClN4/c5-2-1-3(6)9-4(7)8-2/h1H,(H4,6,7,8,9)

Test organisms

Test organisms (species):

Daphnia magna

Results and discussion

Effect concentrations

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

13 mg/L

Any other information on results incl. tables

Endpoint: Short-term toxicity to Daphnia

Dependent variable: Log LC50, where LC50 is the chemical concentration (measured in milligrams per liter) that is expected to kill 50% of a group of organisms (i.e., Daphnia magna) after an exposure of 48h. The final prediction results are converted back to LC50 value (mg/L). In the acute Daphnia toxicity test, the measured effect (immobilization) is associated to the death of the organisms.

Domains: ACD/Percepta provides an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain. In particular: RI < 0.3 (Not Reliable), RI in range 0.3-0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75 (High Reliability). Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. In this case the prediction is considered as moderate reliable since RI is equal to 0.6.

i. descriptor domain: not applicable.

ii. structural fragment domain: not applicable.

iii. mechanism domain: not applicable.

iv. metabolic domain, if relevant: not applicable.

Structural analogues: The similarity of 6-chloropyrimidine-2,4-diamine with respect to the training set compounds was analysed in terms of “property-specific” and structural similarity. Five compounds were identified as analogues of 6 -chloropyrimidine-2,4 -diamine.

Considerations on structural analogues: The identified analogues exhibit moderate similarity with respect to 6-chloropyrimidine-2,4-diamine (similarity index ranging from 0.53 to 0.77), meaning that the target compound is moderately represented in the training set of the model, and experimental LC50 values ranging from 0.10 mg/L to 94 mg/L.

The uncertainty of the prediction is evaluated by ACD/Percepta by means of the reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain. In particular: RI < 0.3 (Not Reliable), RI in range 0.3-0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75 (High Reliability).

Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. In this case the prediction is considered of moderate reliability since RI is equal to 0.6.

Applicant's summary and conclusion

Conclusions:

ACD/Percepta predicted for 6-chloropyrimidine-2,4-diamine an acute LC50 to Daphnia magna equal to 13 mg/L. The prediction is considered of moderate reliability.

Executive summary:

Regulatory purpose: This study was designed to generate estimated in silico (nontesting) data for acute aquatic toxicity in Daphnia magna for 6-chloropyrimidine-2,4-diamine to be used in the regulatory framework of REACH.

Approach for regulatory interpretation of the model result: ACD/Percepta predicted for 6-chloropyrimidine-2,4-diamine an acute LC50 to Daphnia magna equal to 13 mg/L. The prediction is considered of moderate reliability.